Publications by authors named "Fabiana Cacace"

3 Publications

  • Page 1 of 1

Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT.

Front Immunol 2019 14;10:1157. Epub 2019 Jun 14.

Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation, Leiden, Netherlands.

The treatment of paroxysmal nocturnal hemoglobinuria has been revolutionized by the introduction of the anti-C5 agent eculizumab; however, eculizumab is not the cure for Paroxysmal nocturnal hemoglobinuria (PNH), and room for improvement remains. Indeed, the hematological benefit during eculizumab treatment for PNH is very heterogeneous among patients, and different response categories can be identified. Complete normalization of hemoglobin (complete and major hematological response), is seen in no more than one third of patients, while the remaining continue to experience some degree of anemia (good and partial hematological responses), in some cases requiring regular red blood cell transfusions (minor hematological response). Different factors contribute to residual anemia during eculizumab treatment: underlying bone marrow dysfunction, residual intravascular hemolysis and the emergence of C3-mediated extravascular hemolysis. These two latter pathogenic mechanisms are the target of novel strategies of anti-complement treatments, which can be split into terminal and proximal complement inhibitors. Many novel terminal complement inhibitors are now in clinical development: they all target C5 (as eculizumab), potentially paralleling the efficacy and safety profile of eculizumab. Possible advantages over eculizumab are long-lasting activity and subcutaneous self-administration. However, novel anti-C5 agents do not improve hematological response to eculizumab, even if some seem associated with a lower risk of breakthrough hemolysis caused by pharmacokinetic reasons (it remains unclear whether more effective inhibition of C5 is possible and clinically beneficial). Indeed, proximal inhibitors are designed to interfere with early phases of complement activation, eventually preventing C3-mediated extravascular hemolysis in addition to intravascular hemolysis. At the moment there are three strategies of proximal complement inhibition: anti-C3 agents, anti-factor D agents and anti-factor B agents. These agents are available either subcutaneously or orally, and have been investigated in monotherapy or in association with eculizumab in PNH patients. Preliminary data clearly demonstrate that proximal complement inhibition is pharmacologically feasible and apparently safe, and may drastically improve the hematological response to complement inhibition in PNH. Indeed, we envision a new scenario of therapeutic complement inhibition, where proximal inhibitors (either anti-C3, anti-FD or anti-FB) may prove effective for the treatment of PNH, either in monotherapy or in combination with anti-C5 agents, eventually leading to drastic improvement of hematological response.
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http://dx.doi.org/10.3389/fimmu.2019.01157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587878PMC
November 2020

Eltrombopag for post-transplant cytopenias due to poor graft function.

Bone Marrow Transplant 2019 08 24;54(8):1346-1353. Epub 2019 Jan 24.

Hematology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Persistent cytopenia due to poor graft function (PoGF) is a relatively common complication which may affect up to 20% of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Treatment options for PoGF remain limited, and reinfusion of additional HSC is often the only way to rescue hematopoiesis. Here we describe a retrospective single-center experience with the thrombopoietin-mimetic agent eltrombopag for the treatment of PoGF. Thirteen patients have received eltrombopag for either PoGF (n = 12) or primary graft failure (n = 1). In the 12 PoGF patients eltrombopag was started at the median time of 79 days after HSCT, due to persistent thrombocytopenia, with concomitant anemia and neutropenia in 7 and 3 patients, respectively. The treatment was started at the dose of 50 mg per day, and eventually increased up to 150 mg in case of lack of response. Hematological response was seen in 7 patients, with 6 complete responses. Hematological responses were seen both in patients with evidence of immune-mediated pathophysiology, and with possible infectious/iatrogenic causes. In responding patients, eltrombopag was discontinued in 6/7 patients without further relapse. These results suggest that eltrombopag is safe and possibly effective in the setting of the treatment of PoGF, and pave the way for future prospective studies.
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http://dx.doi.org/10.1038/s41409-019-0442-3DOI Listing
August 2019

Ibrutinib as salvage therapy in mantle cell lymphoma with central nervous system involvement in a pretreated unfit patient.

Leuk Lymphoma 2018 07 11;59(7):1734-1737. Epub 2017 Oct 11.

a Department of Clinical Medicine and Surgery , Federico II University Medical School , Naples , Italy.

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http://dx.doi.org/10.1080/10428194.2017.1387910DOI Listing
July 2018